Since a fluorine atom has the largest electronegativity and oxidation potential, the introduction of a fluorine atom into a drug molecule can increase the lipophilicity of the drug and improve the trans-membrane ability of the drug in a living body, without significant alteration of the volume of the drug molecular. Thus, the bioavailability of the drug would be increased. In 1954, Fried and Sabo discovered that 9a-fluoroacetic acid cortisone prepared by introducing a fluorine atom into cortisone acetate exhibited an anti-inflammatory effect about 15 times higher than that of hydrocortisone. For the first time, the fluorine atom was proved to be efficient for increasing the biological activity of a drug. With the development of fluorine chemistry, fluorine atoms are included by increasing drug molecules, such as atorvastatin calcium, levofloxacin, lansoprazole, efavirenz, ezetimibe and so on.
In recent ten to twenty years, a fluorocyclopropane structural unit has been one of hot topics in the international research of fluorinated drug molecules. Increasing bioactive molecules containing fluorocyclopropane structures have been discovered and some of them have entered into clinical research.
Sitafloxacin, as a new broad-spectrum quinolone-based antibacterial drug, has appeared on the market in Japan and will further come into the market in various countries such as China and South Korea in recent years. It has a very broad market prospect. One of the side chains of sitafloxacin is monofluorocyclopropane. The synthesis of this fragment requires a key intermediate (1S, 2S)-2-fluorocyclopropane carboxylic acid. However, it is difficult and high cost for the synthesis of 2-fluorocyclopropane carboxylic acid. As a result, the raw material of sitafloxacin is expensive, which may impair the market promotion thereof. Therefore, it is necessary to develop a novel, highly effective and cost-effective technology for the synthesis of 2-fluorocyclopropane carboxylic acid.
